tbuckley/cabot-search huggingface dataset:
Targeting the interleukin-5 pathway in EGPA: evidence, uncertainties and opportunities
Authors: Alvise Berti, Fabiola Atzeni, Lorenzo Dagna, Stefano Del Giacco, Giacomo Emmi, Carlo Salvarani, Augusto Vaglio
Journal: Annals of the Rheumatic Diseases (2022)

Only a minority of patients with eosinophilic granulomatosis with polyangiitis (EGPA) can be weaned-off glucocorticoids (GC) using conventional treatment strategies. The development of biological agents specifically inhibiting the IL-5 pathway provided the opportunity to treat EGPA by targeting one of the crucial regulators of eosinophils, reducing the GC dose required to control the disease.The anti-IL-5 antibody mepolizumab at the dose of 300 mg/4 weeks has proven to be safe and effective in EGPA. While relapsing patients-who often experience recurrent respiratory manifestations-benefit from this treatment, data are not enough to support its use combined with GC alone in remission induction of severe active forms, or in remission maintenance without conventional immunosuppressants in patients with vasculitic manifestations. Ultimately, the profile of the best candidate for mepolizumab is still unclear.Several real-life reports suggest that mepolizumab at the dose of 100 mg/4 weeks, approved for eosinophilic asthma/chronic rhinosinusitis with nasal polyposis (CRSwNP), effectively maintains remission of EGPA-related asthma and, to a lesser extent, CRSwNP. Preliminary data on the IL-5 pathway-inhibitors benralizumab and reslizumab in EGPA as steroid-sparing agents are also accumulating.Overall, it remains to be proven whether targeting the IL-5 pathway could block progression of organ damage in EGPA, on top of reducing relapses and sparing GC. Other disease-related factors further complicate the understanding of the real anti-IL-5 agent efficacy, such as the lack of a clear definition of remission, of an effective tool to measure disease activity, and of well-defined treat-to-target approaches or goals of treatment.
Graph deep learning for the characterization of tumour microenvironments from spatial protein profiles in tissue specimens
Authors: Zhenqin Wu, Alexandro E. Trevino, Eric Wu, Kyle Swanson, Honesty J. Kim, H. Blaize D’Angio, Ryan Preska, Gregory W. Charville, Piero D. Dalerba, Ann Marie Egloff, Ravindra Uppaluri, Umamaheswar Duvvuri, Aaron T. Mayer, James Zou
Journal: Nature Biomedical Engineering (2022)
Biomarkers associated with the development of comorbidities in patients with atopic dermatitis: A systematic review
Authors: Conor Broderick, Stefanie Ziehfreund, Karin van Bart, Bernd Arents, Kilian Eyerich, Stephan Weidinger, Joseph Rastrick, Alexander Zink, Carsten Flohr
Journal: Allergy (2022)

Abstract Biomarkers associated with the development of comorbidities in atopic dermatitis (AD) patients have been reported, but have not yet been systematically reviewed. Seven electronic databases were searched, from database inception to September 2021. English language randomized controlled trials, prospective and retrospective cohort, and case–control studies that investigated the association between a biomarker and the development of comorbidities in AD patients were included. Two authors independently screened the records for eligibility, one extracted all data, and critically appraised the quality of studies and risk of bias. Fifty six articles met the inclusion criteria, evaluating 146 candidate biomarkers. The most frequently reported biomarkers were filaggrin mutations and allergen specific‐IgE. Promising biomarkers include specific‐IgE and/or skin prick tests predicting the development of asthma, and genetic polymorphisms predicting the occurrence of eczema herpeticum. The identified studies and biomarkers were highly heterogeneous, and associated with predominately moderate‐to‐high risk of bias across multiple domains. Overall, findings were inconsistent. High‐quality studies assessing biomarkers associated with the development of comorbidities in people with AD are lacking. Harmonized datasets and independent validation studies are urgently needed.
Respective roles of non-pharmaceutical interventions in bronchiolitis outbreaks: an interrupted time-series analysis based on a multinational surveillance system
Authors: Lea Lenglart, Naim Ouldali, Kate Honeyford, Zsolt Bognar, Silvia Bressan, Danilo Buonsenso, Liviana Da Dalt, Tisham De, Ruth Farrugia, Ian K. Maconochie, Henriette A. Moll, Rianne Oostenbrink, Niccolo Parri, Damian Roland, Katy Rose, Esra Akyüz Özkan, François Angoulvant, Camille Aupiais, Clarissa Barber, Michael Barrett, Romain Basmaci, Susana Castanhinha, Antonio Chiaretti, Sheena Durnin, Patrick Fitzpatrick, Laszlo Fodor, Borja Gomez, Susanne Greber-Platzer, Romain Guedj, Florian Hey, Lina Jankauskaite, Daniela Kohlfuerst, Ines Mascarenhas, Anna Maria Musolino, Zanda Pučuka, Sofia Reis, Alexis Rybak, Petra Salamon, Matthias Schaffert, Keren Shahar-Nissan, Maria Chiara Supino, Ozlem Teksam, Caner Turan, Roberto Velasco, Ruud G. Nijman, Luigi Titomanlio
Journal: European Respiratory Journal (2022)

Background Bronchiolitis is a major source of morbimortality among young children worldwide. Non-pharmaceutical interventions (NPIs) implemented to reduce the spread of severe acute respiratory syndrome coronavirus 2 may have had an important impact on bronchiolitis outbreaks, as well as major societal consequences. Discriminating between their respective impacts would help define optimal public health strategies against bronchiolitis. We aimed to assess the respective impact of each NPI on bronchiolitis outbreaks in 14 European countries. Methods We conducted a quasi-experimental interrupted time-series analysis based on a multicentre international study. All children diagnosed with bronchiolitis presenting to the paediatric emergency department of one of 27 centres from January 2018 to March 2021 were included. We assessed the association between each NPI and change in the bronchiolitis trend over time by seasonally adjusted multivariable quasi-Poisson regression modelling. Results In total, 42 916 children were included. We observed an overall cumulative 78% (95% CI −100– −54%; p&lt;0.0001) reduction in bronchiolitis cases following NPI implementation. The decrease varied between countries from −97% (95% CI −100– −47%; p=0.0005) to −36% (95% CI −79–7%; p=0.105). Full lockdown (incidence rate ratio (IRR) 0.21 (95% CI 0.14–0.30); p&lt;0.001), secondary school closure (IRR 0.33 (95% CI 0.20–0.52); p&lt;0.0001), wearing a mask indoors (IRR 0.49 (95% CI 0.25–0.94); p=0.034) and teleworking (IRR 0.55 (95% CI 0.31–0.97); p=0.038) were independently associated with reducing bronchiolitis. Conclusions Several NPIs were associated with a reduction of bronchiolitis outbreaks, including full lockdown, school closure, teleworking and facial masking. Some of these public health interventions may be considered to further reduce the global burden of bronchiolitis.
When instrumental inference hides behind seemingly arbitrary conventions
Authors: Edgar Dubourg, Léo Fitouchi, Nicolas Baumard
Journal: Behavioral and Brain Sciences (2022)

We review recent evidence that game rules, rules of etiquette, and supernatural beliefs, that the authors see as "ritualistic" conventions, are in fact shaped by instrumental inference. In line with such examples, we contend that cultural practices that may appear, from the outside, to be devoid of instrumental utility, could in fact be selectively acquired and preserved because of their perceived utility.
BRAF/MEK Dual Inhibitors Therapy in Progressive and Anaplastic Pleomorphic Xanthoastrocytoma: Case Series and Literature Review
Authors: Karolina Kata, Juan C. Rodriguez-Quintero, Octavio D. Arevalo, Jackie J. Zhang, Meenakshi Bidwai Bhattacharjee, Cornelius Ware, Antonio Dono, Roy Riascos-Castaneda, Nitin Tandon, Angel Blanco, Yoshua Esquenazi, Leomar Y. Ballester, Mark Amsbaugh, Arthur L. Day, Jay-Jiguang Zhu
Journal: Journal of the National Comprehensive Cancer Network (2022)

Recurrent and anaplastic pleomorphic xanthoastrocytoma (r&amp;aPXA) is a rare primary brain tumor that is challenging to treat. Two-thirds of PXA tumors harbor a BRAF gene mutation. BRAF inhibitors have been shown to improve tumor control. However, resistance to BRAF inhibition develops in most cases. Concurrent therapy with MEK inhibitors may improve tumor control and patient survival. In this study, we identified 5 patients diagnosed with BRAF -mutated PXA who received BRAF and MEK inhibitors over a 10-year interval at our institution. Patient records were evaluated, including treatments, adverse effects (AEs), outcomes, pathology, next-generation sequencing, and MRI. The median age was 22 years (range, 14–66 years), 60% male, and 60% anaplastic PXA. Median overall survival was 72 months (range, 19–112 months); 1 patient died of tumor-related hemorrhage while off therapy, and the other 4 experienced long-term disease control (21, 72, 98, and 112 months, respectively). Dual BRAF/MEK inhibitors were well tolerated, with only grade 1–2 AEs, including rash, neutropenia, fatigue, abdominal discomfort, and diarrhea. No grade 3–5 AEs were detected. A literature review was also performed of patients diagnosed with BRAF -mutated PXA and treated with BRAF and/or MEK inhibitors through August 2021, with a total of 32 cases identified. The median age was 29 years (range, 8–57 years) and the median PFS and OS were 8.5 months (range, 2–35 months) and 35 months (range, 10–80 months), respectively. The most common AEs were grade 1–2 fatigue and skin rash. Results of this case series and literature review indicate that dual-drug therapy with BRAF and MEK inhibitors for r&amp;aPXA with BRAF V600E mutation may delay tumor progression without unexpected AEs.
Specific targeting of glioblastoma with an oncolytic virus expressing a cetuximab-CCL5 fusion protein via innate and adaptive immunity
Authors: Lei Tian, Bo Xu, Yuqing Chen, Zhenlong Li, Jing Wang, Jianying Zhang, Rui Ma, Shuai Cao, Weidong Hu, E. Antonio Chiocca, Balveen Kaur, Michael A. Caligiuri, Jianhua Yu
Journal: Nature Cancer (2022)
NCCN Guidelines® Insights: Gastrointestinal Stromal Tumors, Version 2.2022
Authors: Margaret von Mehren, John M. Kane, Richard F. Riedel, Jason K. Sicklick, Seth M. Pollack, Mark Agulnik, Marilyn M. Bui, Janai Carr-Ascher, Edwin Choy, Mary Connelly, Sarah Dry, Kristen N. Ganjoo, Ricardo J. Gonzalez, Ashley Holder, Jade Homsi, Vicki Keedy, Ciara M. Kelly, Edward Kim, David Liebner, Martin McCarter, Sean V. McGarry, Nathan W. Mesko, Christian Meyer, Alberto S. Pappo, Amanda M. Parkes, Ivy A. Petersen, Matthew Poppe, Scott Schuetze, Jacob Shabason, Matthew B. Spraker, Melissa Zimel, Mary Anne Bergman, Hema Sundar, Lisa E. Hang
Journal: Journal of the National Comprehensive Cancer Network (2022)

Gastrointestinal stromal tumors (GIST) are the most common type of soft tissue sarcoma that occur throughout the gastrointestinal tract. Most of these tumors are caused by oncogenic activating mutations in the KIT or PDGFRA genes. The NCCN Guidelines for GIST provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with these tumors. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including revised systemic therapy options for unresectable, progressive, or metastatic GIST based on mutational status, and updated recommendations for the management of GIST that develop resistance to specific tyrosine kinase inhibitors.
Revisiting an extant framework: Concerns about culture and task generalization
Authors: Frankie T. K. Fong, Mark Nielsen, Cristine H. Legare
Journal: Behavioral and Brain Sciences (2022)

The target article elaborates upon an extant theoretical framework, "Imitation and Innovation: The Dual Engines of Cultural Learning." We raise three major concerns: (1) There is limited discussion of cross-cultural universality and variation; (2) overgeneralization of overimitation and omission of other social learning types; and (3) selective imitation in infants and toddlers is not discussed.
Is there a need to distinguish instrumental copying behavior from traditions?
Authors: Thomas R. Zentall
Journal: Behavioral and Brain Sciences (2022)

Abstract The authors make a distinction between instrumental copying behavior in which there is a clear reward for the copying behavior and social copying (traditions) in which the rewards for copying are less clear. However, I see no reason to distinguish between the two. We are social animals, for whom copying traditions have important rewards, those of affiliation.
Cultural evolution is not independent of linguistic evolution and social aspects of language use
Authors: Mathias Scharinger, Luise M. Erfurth
Journal: Behavioral and Brain Sciences (2022)

The bifocal stance theory (BST) focuses on cultural evolution without alluding to associated processes in linguistic evolution and language use. The authors briefly comment on language acquisition but leave underexplored the applicability of BST to linguistic evolution, to changes of language representations, and to possible consequences for constructing social identity, based on, for example, collective resilience processes within language communities.
What is the simplest model that can account for high-fidelity imitation?
Authors: Joel Z. Leibo, Raphael Köster, Alexander Sasha Vezhnevets, Edgar A. Duénez-Guzmán, John P. Agapiou, Peter Sunehag
Journal: Behavioral and Brain Sciences (2022)

What inductive biases must be incorporated into multi-agent artificial intelligence models to get them to capture high-fidelity imitation? We think very little is needed. In the right environments, both instrumental- and ritual-stance imitation can emerge from generic learning mechanisms operating on non-deliberative decision architectures. In this view, imitation emerges from trial-and-error learning and does not require explicit deliberation.
SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines
Authors: John E. Bowen, Young-Jun Park, Cameron Stewart, Jack T. Brown, William K. Sharkey, Alexandra C. Walls, Anshu Joshi, Kaitlin R. Sprouse, Matthew McCallum, M. Alejandra Tortorici, Nicholas M. Franko, Jennifer K. Logue, Ignacio G. Mazzitelli, Annalee W. Nguyen, Rui P. Silva, Yimin Huang, Jun Siong Low, Josipa Jerak, Sasha W. Tiles, Kumail Ahmed, Asefa Shariq, Jennifer M. Dan, Zeli Zhang, Daniela Weiskopf, Alessandro Sette, Gyorgy Snell, Christine M. Posavad, Najeeha Talat Iqbal, Jorge Geffner, Alessandra Bandera, Andrea Gori, Federica Sallusto, Jennifer A. Maynard, Shane Crotty, Wesley C. Van Voorhis, Carlos Simmerling, Renata Grifantini, Helen Y. Chu, Davide Corti, David Veesler
Journal: Science Immunology (2022)

Numerous safe and effective coronavirus disease 2019 vaccines have been developed worldwide that use various delivery technologies and engineering strategies. We show here that vaccines containing prefusion-stabilizing S mutations elicit antibody responses in humans with enhanced recognition of S and the S
Coevolution of religious and political authority in Austronesian societies
Authors: Oliver Sheehan, Joseph Watts, Russell D. Gray, Joseph Bulbulia, Scott Claessens, Erik J. Ringen, Quentin D. Atkinson
Journal: Nature Human Behaviour (2022)

Authority, an institutionalized form of social power, is one of the defining features of the large-scale societies that evolved during the Holocene. Religious and political authority have deep histories in human societies and are clearly interdependent, but the nature of their relationship and its evolution over time is contested. We purpose-built an ethnographic dataset of 97 Austronesian societies and used phylogenetic methods to address two long-standing questions about the evolution of religious and political authority: first, how these two institutions have coevolved, and second, whether religious and political authority have tended to become more or less differentiated. We found evidence for mutual interdependence between religious and political authority but no evidence for or against a long-term pattern of differentiation or unification in systems of religious and political authority. Our results provide insight into how political and religious authority have worked synergistically over millennia during the evolution of large-scale societies.
Conformity versus transmission in animal cultures
Authors: Andrew Whiten
Journal: Behavioral and Brain Sciences (2022)

The principal contrasts that Jagiello et al. highlight are among many cultural transmission biases we now know of. I suggest they are also reflected more widely in social learning decisions among nonhuman animal cultures governing whether cultural innovations spread, or are instead over-ridden by immigrants' conformity in their new group. Such conformity may serve either informational or social-integrative functions.
Single-cell RNA-seq uncovers cellular heterogeneity and provides a signature for paediatric sleep apnoea
Authors: Rene Cortese, Taylor S. Adams, Kylie H. Cataldo, Justin Hummel, Naftali Kaminski, Leila Kheirandish-Gozal, David Gozal
Journal: European Respiratory Journal (2022)

Background Obstructive sleep apnoea (OSA) is a highly prevalent disease and a major cause of systemic inflammation leading to neurocognitive, behavioural, metabolic and cardiovascular dysfunction in children and adults. However, the impact of OSA on the heterogeneity of circulating immune cells remains to be determined. Methods We applied single-cell transcriptomics analysis (scRNA-seq) to identify OSA-induced changes in transcriptional landscape in peripheral blood mononuclear cell (PBMC) composition, which uncovered severity-dependent differences in several cell lineages. Furthermore, a machine-learning approach was used to combine scRNAs-seq cell-specific markers with those differentially expressed in OSA. Results scRNA-seq demonstrated OSA-induced heterogeneity in cellular composition and enabled the identification of previously undescribed cell types in PBMCs. We identified a molecular signature consisting of 32 genes, which distinguished OSA patients from various controls with high precision (area under the curve 0.96) and accuracy (93% positive predictive value and 95% negative predictive value) in an independent PBMC bulk RNA expression dataset. Conclusion OSA deregulates systemic immune function and displays a molecular signature that can be assessed in standard cellular RNA without the need for pre-analytical cell separation, thereby making the assay amenable to application in a molecular diagnostic setting.
Comprehensive transcriptional variability analysis reveals gene networks regulating seed oil content of Brassica napus
Authors: Zengdong Tan, Yan Peng, Yao Xiong, Feng Xiong, Yuting Zhang, Ning Guo, Zhuo Tu, Zhanxiang Zong, Xiaokun Wu, Jiang Ye, Chunjiao Xia, Tao Zhu, Yinmeng Liu, Hongxiang Lou, Dongxu Liu, Shaoping Lu, Xuan Yao, Kede Liu, Rod J. Snowdon, Agnieszka A. Golicz, Weibo Xie, Liang Guo, Hu Zhao
Journal: Genome biology (2022)

Abstract Background Regulation of gene expression plays an essential role in controlling the phenotypes of plants. Brassica napus ( B. napus ) is an important source for the vegetable oil in the world, and the seed oil content is an important trait of B. napus . Results We perform a comprehensive analysis of the transcriptional variability in the seeds of B. napus at two developmental stages, 20 and 40 days after flowering (DAF). We detect 53,759 and 53,550 independent expression quantitative trait loci (eQTLs) for 79,605 and 76,713 expressed genes at 20 and 40 DAF, respectively. Among them, the local eQTLs are mapped to the adjacent genes more frequently. The adjacent gene pairs are regulated by local eQTLs with the same open chromatin state and show a stronger mode of expression piggybacking. Inter-subgenomic analysis indicates that there is a feedback regulation for the homoeologous gene pairs to maintain partial expression dosage. We also identify 141 eQTL hotspots and find that hotspot87-88 co-localizes with a QTL for the seed oil content. To further resolve the regulatory network of this eQTL hotspot, we construct the XGBoost model using 856 RNA-seq datasets and the Basenji model using 59 ATAC-seq datasets. Using these two models, we predict the mechanisms affecting the seed oil content regulated by hotspot87-88 and experimentally validate that the transcription factors, NAC13 and SCL31, positively regulate the seed oil content. Conclusions We comprehensively characterize the gene regulatory features in the seeds of B. napus and reveal the gene networks regulating the seed oil content of B. napus .
Rare and common genetic determinants of metabolic individuality and their effects on human health
Authors: Praveen Surendran, Isobel D. Stewart, Victoria P. W. Au Yeung, Maik Pietzner, Johannes Raffler, Maria A. Wörheide, Chen Li, Rebecca F. Smith, Laura B. L. Wittemans, Lorenzo Bomba, Cristina Menni, Jonas Zierer, Niccolò Rossi, Patricia A. Sheridan, Nicholas A. Watkins, Massimo Mangino, Pirro G. Hysi, Emanuele Di Angelantonio, Mario Falchi, Tim D. Spector, Nicole Soranzo, Gregory A. Michelotti, Wiebke Arlt, Luca A. Lotta, Spiros Denaxas, Harry Hemingway, Eric R. Gamazon, Joanna M. M. Howson, Angela M. Wood, John Danesh, Nicholas J. Wareham, Gabi Kastenmüller, Eric B. Fauman, Karsten Suhre, Adam S. Butterworth, Claudia Langenberg
Journal: Nature Medicine (2022)

Abstract Garrod’s concept of ‘chemical individuality’ has contributed to comprehension of the molecular origins of human diseases. Untargeted high-throughput metabolomic technologies provide an in-depth snapshot of human metabolism at scale. We studied the genetic architecture of the human plasma metabolome using 913 metabolites assayed in 19,994 individuals and identified 2,599 variant–metabolite associations ( P &lt; 1.25 × 10 −11 ) within 330 genomic regions, with rare variants (minor allele frequency ≤ 1%) explaining 9.4% of associations. Jointly modeling metabolites in each region, we identified 423 regional, co-regulated, variant–metabolite clusters called genetically influenced metabotypes. We assigned causal genes for 62.4% of these genetically influenced metabotypes, providing new insights into fundamental metabolite physiology and clinical relevance, including metabolite-guided discovery of potential adverse drug effects ( DPYD and SRD5A2 ). We show strong enrichment of inborn errors of metabolism-causing genes, with examples of metabolite associations and clinical phenotypes of non-pathogenic variant carriers matching characteristics of the inborn errors of metabolism. Systematic, phenotypic follow-up of metabolite-specific genetic scores revealed multiple potential etiological relationships.
Tradition–invention dichotomy and optimization in the field of science
Authors: Mukta Watve, Milind Watve
Journal: Behavioral and Brain Sciences (2022)

The central idea of the bifocal stance theory (BST) by Jagiello et al. has substantial relevance to scientific research. Both tradition-following and exploration-innovation are important in science and researchers subconsciously try to optimize their strategies. We outline three important dimensions of this optimization and argue that attempts to understand this complex process can help us design better science education, research training, investigation, and science publication.